National Center for Tumor Diseases, University Hospital Heidelberg, German Cancer Research Center, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.
Department of Obstetrics and Gynecology, University Hospital Heidelberg, Heidelberg, Germany.
Target Oncol. 2020 Aug;15(4):415-428. doi: 10.1007/s11523-020-00730-0.
Triple-negative breast cancer constitutes ~ 15% of all breast cancer subtypes. Because of the negative hormone receptor and human epidermal growth factor receptor 2 status, therapy is mainly based on chemotherapy with a poor median overall survival in the metastatic setting of ~ 18 months. Compared to other breast cancer subtypes, triple-negative breast cancer is characterized by a higher mutational load, which renders the tumor immunogenic and amenable to immunotherapeutic intervention. Based on the promising results of immunotherapy in other cancer entities, including melanoma or non-small cell lung cancer, a vast number of studies are currently assessing immunotherapeutic approaches in patients with triple-negative breast cancer. While monotherapies with antibodies against programmed death-1 and programmed death ligand-1 have shown little efficacy in patients with heavily pretreated metastatic triple-negative breast cancer, treatment efficacy likely depends on the therapeutic setting, the treatment line, and the combination of immunotherapies with other anticancer drugs. Several studies are currently evaluating the safety and efficacy of immune checkpoint inhibition in combination with chemotherapy, angiogenesis inhibitors, poly(ADP-ribose) polymerase inhibitors, as well as radiotherapy in the metastatic and (neo-)adjuvant settings. The US Food and Drug Administration approval of nab-paclitaxel in combination with atezolizumab in 2019 presented a landmark therapeutic development for patients with triple-negative breast cancer, given the limited treatment options available for this highly aggressive disease. In this review, we provide an overview on important ongoing and completed immunotherapeutic studies in triple-negative breast cancer and their possible implications for clinical practice.
三阴性乳腺癌约占所有乳腺癌亚型的 15%。由于激素受体和人表皮生长因子受体 2 状态为阴性,治疗主要基于化疗,转移性疾病的中位总生存期约为 18 个月,预后较差。与其他乳腺癌亚型相比,三阴性乳腺癌具有更高的突变负荷,这使其具有免疫原性,可接受免疫治疗干预。基于免疫疗法在其他癌症实体中的良好效果,包括黑色素瘤或非小细胞肺癌,目前有大量研究正在评估免疫疗法在三阴性乳腺癌患者中的应用。尽管针对程序性死亡受体 1 和程序性死亡配体 1 的单克隆抗体在经大量预处理的转移性三阴性乳腺癌患者中的疗效有限,但治疗效果可能取决于治疗环境、治疗线以及免疫疗法与其他抗癌药物的联合应用。目前,多项研究正在评估免疫检查点抑制剂联合化疗、血管生成抑制剂、聚(ADP-核糖)聚合酶抑制剂以及放疗在转移性和(新)辅助治疗环境中的安全性和疗效。美国食品和药物管理局于 2019 年批准了 nab-紫杉醇联合阿替利珠单抗用于治疗三阴性乳腺癌,这是该高度侵袭性疾病治疗的一个重要进展,因为该疾病的治疗选择有限。在这篇综述中,我们概述了三阴性乳腺癌中正在进行和已完成的重要免疫治疗研究及其对临床实践的可能影响。